persp ctive
september 20
15
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no
34
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HEALTH
persp ctive
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Through Perspective, CIRAD provides the opportunity to explore new avenues for discussion and action based on research, without presenting an institutional position.
34
Integrated management of insect vectors of human
and animal diseases
Developing
genetic control
Jérémy BOUYER
The evolution of insecticide resistance in insect vectors of human and animal
diseases and the introduction of exotic vectors to new territories, in a context of
tighter regulations on approved molecules, call for the development of new pest
control methods.
Among these new methods, genetic control shows promise, as demonstrated by
the tsetse fly eradication project in Senegal. It nevertheless requires complementary
studies combining public and private research. Moreover, it must be combined
with other methods of pest control – chemical, physical and biological – within an
integrated management framework.
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wareness of the toxicity of insecticides to living organisms and ecosystems is leading a growing number of countries to reduce the number of approved molecules. For example, in 2014, the European Union was still authorising only four classes of vector control insecticides, and only three new classes are being developed, for operational use no earlier than 2019. Moreover, resistance to pyrethroids, the most common class used against insects, is spreading, which could result in its disuse in the short-term.These regulations are being tightened amid growing pressure from insect vectors of human and animal diseases. This pressure is explained
by greater resistance to insecticides, but also by global factors, such as climate change or growth in trade. These global factors foster the invasion of new territories by exotic vectors. For example, the midge Culicoides imicola, a vector of blue-tongue disease native to tropical Africa, is invad-ing Europe from the south. This disease caused an unprecedented health crisis in the French ruminant sector between 2006 and 2008. The tiger mosquito, Aedes albopictus, which is native to Asia and a major vector of arboviruses in humans, caused indigenous cases of dengue and chikungunya in mainland France in 2014. In-novations are therefore urgently required in the field of vector control.
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Integrated control: a core challenge associating chemical, biological and mechanical methods, with help from modelling>
Use of transgenic insects requires a case-by-case analysisNeutralising females
Genetic control is one of the methods that could replace insecticide use. It consists in the large-scale rearing of insects – whether genetically modified or not –, with the subsequent release of males in order for them to sterilise females or to transfer to females mutations that are either lethal or impede their ability to transmit a dis-ease. One variant consists in contaminating females with symbionts (organisms living in symbiosis with insects) – whether modified or not –, which sterilise females or block the trans-mission of the disease.
The sterile insect technique (SIT) is the first method based on this strategy: the males are irradiated and transmit to the females with which they mate sperm cells carrying lethal mutations. This technique has been used suc-cessfully in the control of a number of insect pests or vectors, such as species of fruit flies, the screw-worm fly and the tsetse fly.
The use of genetically modified insects – or transgenic males – to transmit a mutation to females has the advantage of avoiding the need for irradiation, which is often based on the use of radioactive sources. Mutations can block the ability to transmit a disease, turn females into inoffensive males, or even destroy the targeted insect. However, this technique is less acceptable to society because of its potential biological risks, especially the transfer of genes to non-targeted insects. This risk depends on the genetic mechanisms used, and in particular on their potential for dissemination. It is thus lower for the transfer of dominant lethal mutations (sim-ilar to that of the sterile insect technique) than for the use of symbionts.
Supporting genetic control
through field research
In Senegal, a tsetse fly eradication project has been implemented in the Niayes area, based on an integrated strategy, the approach underpin-ning the IVEMA research project, “Integrated vector management: innovating to improve con-trol and reduce environmental impacts” (see box p. 4). Because of its climate, this area near Dakar is suitable for the intensification of cattle farm-ing, for which there is high demand, especially for milk (the zone is home to almost 80% of the population of Senegal). However, an isolated tsetse fly population maintains the transmission of trypanosomosis, reducing milk and meat
production and animal labour by around 30% and hindering intensification. By controlling the disease, the project aims to enable communities of livestock farmers who so wish to adopt more productive breeds and to reduce herd sizes in a context in which land constraints limit this size and pose feeding problems.
Each stage of the project involved methodo-logical and technomethodo-logical developments. Habi-tats suitable to the tsetse fly were identified by remote sensing based on a population distribu-tion model. Using this model, the number of traps needed per km² to suppress tsetse popula-tions by more than 95% was reduced by 30%. This model was also used to set the densities of sterile males to be released (10 sterile males per km² if the habitat is unsuitable; 100 if it is suit-able). These sterile males were produced and irradiated in Burkina Faso at CIRDES (Centre International de Recherche-Développement sur l’Elevage en Zone Subhumide), and in Slovakia, by the Slovak Academy of Sciences. They were transported to Senegal by express delivery under regulatory and optimal conditions to guarantee their survival (in particular, a temperature of 10°C). They were then reared for six days in an insectarium at ISRA (Institut Sénégalais de Recherches Agricoles), before being released by an automatic machine loaded onto a gyrocopter (see Photo, next page). This machine, developed by a Mexican company, is piloted by a geo-graphic information system (GIS) that can adjust the density of sterile males to be released in order to achieve the objective. Installed on an android tablet, this GIS enables the pilot to concentrate on following release lines, with the machine automatically beginning the release upon entering the target zone, and ceasing upon exit.
This eradication campaign opens up economic and environmental opportunities, and an ex-ante cost-benefit analysis has demonstrated its profitability. For a total cost of 6 400 euros per km2 to the government of Senegal and
interna-tional donors for permanent tsetse fly eradica-tion, after 10 to 20 years (depending on the innovation scenario), the project would generate 2 800 euros per km2 per year in additional sales
of animal products (milk and meat) for the com-munity of beneficiary livestock farmers. IVEMA places integrated pest control at the core of its strategy, associating chemical, biological and mechanical methods according to the conditions for action, and optimising their association
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New cooperation strategies are needed, implying attitude changes among partnersthrough a significant modelling element. By supporting genetic control through field research, this project has succeeded in reducing the use of insecticide treatments (in terms of their frequency or dosage) and in developing the sterile insect technique.
The innovative elements of this project are cur-rently being transferred to other tsetse fly erad-ication projects in Africa, within the framework of PATTEC (the African Union Pan African Tsetse and Trypanosomosis Eradication Cam-paign). Many of them will also help to improve mosquito control in other parts of the world. However, implementing SIT requires sufficient quantities of sterile males to overwhelm the target population, and also a number of sterile males exceeding that of wild males. To overcome these obstacles, a variant of SIT, known as “boosted SIT”, has been developed. It aims to reduce by 90 to 99% the quantity of sterile males needed to control or eradicate a target popula-tion. In this variant, sterile males are considered as a specific means of contaminating females with a control agent. This agent may be an active substance, bacteria, a fungus or a virus, or even recombinant versions of these pathogens. But this is dependent on two conditions: avoiding contamination of species other than the target species; and avoiding dissemination after the
insect’s death. Developing this kind of biocide implies a risk assessment, guaranteed by close cooperation between public research and indus-tries.
Involving public research
and industries
Collaboration between public research and pri-vate research is needed not only for the large-scale use of transgenic insects, but also for the development of new control methods and to guarantee their safety and sustainability. All partners will benefit from this.
The large-scale use of sterile insects implies mobilising extensive research and development programmes, such as the ones leading to the eradication of the screw-worm, an insect of veterinary concern, in North America, Central America and Libya, and of the Mediterranean fruit fly, of agricultural concern, in Mexico – this fly is the subject of an SIT pest control pro-gramme in Spain. However, public research cannot implement these programmes alone, but can contribute to them by conducting the oper-ational research essential to their optimisation and their success.
As for industries, they are faced with stricter regulations limiting the number of approved molecules and with the shorter lifespan of these molecules because of resistance. It is therefore in their interest to invest in the development of new non-toxic control methods, and to deploy these within an integrated pest control frame-work, taking into account lessons learned from past experience. Public research can make sig-nificant contributions to both processes. Another area of collaboration is the assessment and management of the impact of chemical molecules used and of risks associated with the use of transgenic insects. To ensure that chemi-cal molecules can be used in the long term, their effects on vector populations, as well as the changes caused, must be evaluated. As for trans-genic insects, their use is booming. Releases of
Aedes aegypti mosquitoes (another major vector
of arboviruses) that have been genetically mod-ified to atrophy the wings of female descendants and to prevent them from flying, have succeeded in eliminating more than 90% of target popula-tions in parts of the Cayman Islands, Panama and Brazil. Testing in natural habitats has been authorised in Malaysia, Mexico and the United States, while trials under controlled conditions
In Senegal, tsetse fly eradication improves cattle producti-vity (pedal of gyrocopter releasing sterile tsetse males over
transhumant zebus between baobabs in the Niayes area in Senegal) © J. Bouyer.
A few words about… Jérémy BOUYER
is a veterinary entomologist at CIRAD. He has been in charge of the Vectors team within the CMAEE research unit (Emerging and Exotic Animal Disease Control) since 2009 (http:// umr-cmaee.cirad.fr/) and is
associated with the INTERTRYP research unit (Host-Vector-Parasite-Environment Interactions in Neglected Tropical Diseases due to Trypanosomatids). After CIRDES (Burkina Faso) from 2001 to 2008, he worked at ISRA (Senegal) from 2009 to 2015 to support the tsetse fly eradication project in the Niayes area, before being posted to Ethiopia. He received the Agence Universitaire de la Francophonie 2015 award for young researchers in the “Science and medicine” category. jeremy.bouyer@cirad.fr
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partners. Industries are invited to take risks and to accept the need to phase out their reliance on chemicals in favour of diversified strategies. And researchers need to open up to industries in order to turn their inventions into innovations. Although genetic control has potential that must be exploited, no technique should be auto-matically ruled out, and it is essential to analyse the advantages, disadvantages and risks associ-ated with each one. This implies gaining further knowledge of the ecology of target vector popu-lations, but also of the socio-ecosystems con-cerned by vector control. It will then be possible to achieve an optimal combination of several different methods, with the help of modelling processes. <
have been authorised in four European countries including France, and an application is pending for testing in natural habitats in Spain. More-over, in France, the Plan Santé Environnement (PNSE 3 – environmental health plan) 2015-2019 encourages the development of research on the sterile insect technique for mosquitoes. The use of transgenic insects therefore requires a case-by-case analysis of risks, since the risk depends on the genetic mechanisms used, and in particular on their potential for dissemina-tion. In Europe, this analysis can be based on EFSA (European Food Safety Authority) rec-ommendations.
New collaboration strategies are therefore required, involving a change of attitude among
This Perspective stems from the IVEMA project, financed within the framework of ANR funding for the Institut Carnot Santé Animale (ICSA) excellence network, and the tsetse fly eradication project in Senegal, coordinated by the Direction des Services Vétérinaires du Sénégal, in partner-ship with the Institut Sénégalais de Recherches Agricoles, the joint FAO-IAEA division on insect pest and vector control, and CIRAD. In addition, IVEMA has established partnerships with private companies: Mubarqui, a Mexican company that developed the automatic machine for the aerial release of sterile males; the pharmaceutical groups Ceva Santé Animale and Virbac; the French start-up Long Lasting Innovation (L2I); and the com-pany Savana.
At Expo Milano 2015, the tsetse fly eradication project won second prize in the category “Best sustainable development practices in small rural communities”, as an example of ecological inten-sification.
This research has resulted in the following publica-tions:
Bouyer F., M. T. Seck, A. Dicko, B. Sall, M. Lo, M. Vreysen, E. Chia, J. Bouyer & A. Wane, 2014. Ex-ante cost-benefit analysis of tsetse eradication in the Niayes area of Senegal. PloS Negl. Trop. Dis. 8: e3112.
Bouyer J. & T. Lefrançois, 2014. Boosting the sterile insect technique to control mosquitoes. Trends Parasitol. 30: 271-273.
Dicko A. H., R. Lancelot, M. T. Seck, L. Guerrini, B. Sall, M. Lo, M. J. B. Vreysen, T. Lefrançois, F. Williams, S. L. Peck & J. Bouyer, 2014. Using species distribution models to optimize vector control: the tsetse eradication campaign in Sene-gal. Proceedings of the National Academy of Sciences 111: 10149-10154.
It has also given rise to a presentation (www.isntd. org/#/isntd-bites-15-bouyer/4589861215) and an interview (www.isntd.org/#/isntd-bites-15-interv-bouyer/4589652779) that reflects the opinion of the author and not that of CIRAD, and can be found online on the website of the International Society for Neglected Tropical Diseases.
FIND OUT MORE
Alphey L., 2014. Genetic Control of Mosquitoes. Annu. Rev. Entomol. 59: 205 (for a review of the potential for dissemination of different genetic mechanisms).
McGraw E. A. & S. L. O’Neill, 2013. Beyond insecticides: new thinking on an ancient problem. Nat Rev Microbiol 11: 181-193 (for a review of credible alternatives to insecticides).
Suckling D. M., P. C. Tobin, D. G. McCullough & D. A. Herms. 2012. Combining tactics to exploit Allee effects for eradication of alien insect populations. J. Econ. Entomol. 105: 1-13 (for a review of the integration of different pest control methods).
